tDCS, Stress and Risk for Schizophrenia (3S)

Effects of Transcranial Direct Current Stimulation on Stress Reactivity and Decision Making in Unaffected Siblings of Patients With Schizophrenia

An exacerbated response to stress mediated by activation of the Hypothalamo-Pituitary-Adrenocortical (HPA) axis is thought to play an important role in the onset, worsening and relapse of schizophrenia. Subjects at risk for schizophrenia (unaffected siblings of patients) displayed an intermediate hyperreactivity to stress as compared with patients and healthy controls.

Symptoms of schizophrenia can be reduced with noninvasive brain stimulation (NIBS) applied over the dorsolateral prefrontal cortex (DLPFC). Importantly, this same DLPFC NIBS protocol can modulate decision making processes and modulate biological reactivity to stress by decreasing salivary cortisol concentration in acute stress condition.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Device: Transcranial stimulation in direct current

Detailed Description

The objective of this project is to evaluate how the modulation of DLPFC activity in acute stress condition influences decision-making in unaffected siblings of patients with schizophrenia.

Methods: 30 unaffected siblings of patients with schizophrenia will be enrolled and randomized into 2 groups. 15 subjects will receive active tDCS (2mA, 30 min, anode left DLPFC, cathode right DLPFC) and 15 will receive sham tDCS.

tDCS procedure: There is a total of 30 minutes of stimulation at the intensity of 2mA (ramp up and ramp down: 30 sec). Sham stimulation consists in delivering 1 minute of real stimulation. The stimulation site (DLPFC) will be anatomically determined according to 10/20 EEG system (F3 & F4). This procedure is in accordance with international guidelines for safety. Safety and blinding will be assessed using specific tools at the end of the protocol.

Stress paradigm: In order to induce moderate stress in humans in laboratory condition, the investigators will use the Maastricht Acute Stress Test (MAST). This test is a combination between physical (hand immersion in cold water) and cognitive (arithmetic calculation) stress. Test will start 5 minutes after the beginning of stimulation session.

Decision-making paradigm: The decision-making task will be performed before and after the MAST (during the stimulation) in order to compare changes induce by stress and/or stimulation. The choose test is the Delay Discounting Task (DDT) permitting a measure of decision-making, reward seeking and impulsivity.

Stress measure: Saliva samples will be collected using a Salivette®, samples will be stored frozen (- 20°C). Saliva cortisol levels will be measured by ELISA. The investigators also will measure heart rate, systolic and diastolic blood pressures at each time of saliva extraction (each 15 minutes, 1st sample at 9:00 am, please see figure 1). Anxiety will be assessed using the State-Trait Anxiety Inventory (STAI) before and after stimulation

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron Cedex, France, 69678
    • Centre Hospitalier Le Vinatier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 26 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject to genetic risk of schizophrenia, related first-degree schizophrenic patient
• Man and woman
• Age between 18 and 30 years old

Exclusion Criteria:

• Contraindications to the practice of the tDCS, for safety measure, we will use the same contraindications as the practice of the Magnetic resonance imaging
• Psychiatric disorder on axis I of DSM 5
• Pregnant or nursing women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Transcranial stimulation in direct current(tDCS)active; 30 minutes of active Transcranial stimulation in direct current	Device: Transcranial stimulation in direct current; tDCS (2mA, 30 minutes with the anode at the left DLPFC and the cathode at the right DLPFC) active or placebo
Placebo Comparator: Transcranial stimulation in direct current(tDCS) placebo; 30 minutes of placebo stimulation	Device: Transcranial stimulation in direct current; tDCS (2mA, 30 minutes with the anode at the left DLPFC and the cathode at the right DLPFC) active or placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortisol	Salivary cortisol will be analyzed, using Salivette tubes	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decision-making capacities	Decision-making capacities will be measured using a computerized version of the delay discounting task in which participants have to choose between 2 rewards	6 mois
electroencephalography	EEG will be acquired twice. It consists in an at rest recording of EEG 64 channels, eyes closed to measure spectral power intensities	6 mois

Collaborators and Investigators

• Sponsor: Hôpital le Vinatier
• Investigators: Principal Investigator: D AMATO THIERRY, MD - PhD, CH Le Vinatier

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2019
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: tDCS, non invasive brain stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 2017-A00850-53

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No